Retinoblastoma is a rare intraocular cancer in children treated either by removing the eye or giving the child systemic chemotherapy with its attendant toxicity and marginal efficacy for sustained intraocular remission. The episcleral device is a novel system for facilitating the sustained local delivery of therapeutic agents, including chemotherapeutic formulations, directly to the interior of the eye while sequestering these agents from washout to peripheral circulation and protecting sensitive periocular tissues. Inside the impermeable silicone episcleral device, the contents of the drug reservoir are maintained in direct contact with a broad expanse of the outer surface of the eye wall (the episclera), greatly facilitating the net passive unidirectional transscleral diffusion of these agents to the intraocular tumor inside the eye. Delivery from the episcleral exoplant may be sustained for months to years depending on the drug formulation. This RC3 grant requests funding to support clinical trials in patients with advanced unilateral retinoblastoma prescheduled to have an eye surgically removed. Thus this trial will be salvage therapy. Demonstration of safety, tolerability and efficacy will allow 3T Ophthalmics to rapidly bring to market a paradigm change for the treatment of chronic intraocular diseases. PUBLIC HEALTH RELEVANCE: This application requests funding to support the efforts of 3T Ophthalmics to complete clinical trials of their episcleral delivery system that provides therapeutic agents by sequestered passive diffusion across the surface of the eye. Specifically funds requested will support Phase I and Phase II clinical trials of episcleral formulations of carboplatin and topotecan in eyes of children with advanced intraocular retinoblastoma (all IND enabling studies and clinical supplies are covered by a recently awarded NCI-RAID grant). If local targeted episcleral delivery of these agents can safely reduce or eliminate the need for enucleation, systemic chemotherapy, and radiotherapy in eyes with this orphan childhood cancer, then this approach has potential to significantly improve the delivery and reduce the costs of health-care in retinoblastoma as well in many other ophthalmic diseases.